The objectives of this proposal are to examine the effect of viral infection on macrophages in greater detail, using the alveolar macrophage and SIV as a basis of study. Specifically, the aims of this proposal are to: 1) to study the microenvironmental influences of cytokines and activation agents on the efficiency of viral replication within SIV-infected alveolar macrophages, 2) to study the function of SIV-infected alveolar macrophages, as determined by their ability to present antigen and participate in autologous mixed lymphocyte reactions, ability to phagocytize and kill bacteria, ability to perform cytotoxic functions against neoplastic and parasitic targets, and the ability to produce cytokines and immunoregulatory molecules upon stimulation, 3) study any alterations in macrophage-related gene expression resulting from SIV infection and investigate the molecular basis for these alterations, 4) study the in vivo significance of macrophage tropism by comparing the pathogenic potential of SIV isolates that propagate well within macrophages in vitro with isolates that do not grow at all within this particular cell, and 5) investigate the molecular determinants responsible for the growth of SIV within macrophages.